高脂膳食诱导的胰岛素抵抗在血管内皮细胞损伤中的作用及机制研究

项目名称： 高脂膳食诱导的胰岛素抵抗在血管内皮细胞损伤中的作用及机制研究

项目编号： No.81472981

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 孙长颢

作者单位： 哈尔滨医科大学

项目金额： 75万元

中文摘要： 我国心血管疾病(CVD)的发病率持续上升，是导致我国居民死亡的首要病因。动脉粥样硬化（AS）是公认的引起CVD的主要原因，其发病机制复杂，至今尚未完全明确。在众多影响因素中，膳食因素与AS的发生密切相关。研究表明高脂膳食模式引发的胰岛素抵抗是AS及CVD的独立风险因素。胰岛素及游离脂肪酸（FFA）水平的上升是胰岛素抵抗的重要病理特征。现有针对胰岛素抵抗与AS关系的研究主要围绕FFA的脂毒性作用开展，而胰岛素本身对CVD影响的报道较少，胰岛素与FFA的协同作用更未见报道。FFA诱导的血管内皮损伤是AS发生的重要病理基础。我们前期研究表明胰岛素联合软脂酸可显著加重其引起的血管内皮细胞凋亡及粘附因子表达的增加。因此，本项目将通过体内、外实验相结合的方式探讨胰岛素协同FFA对血管内皮损伤的影响，并阐明其分子机制，为揭示动脉粥样硬化的发病机制提供新的理论依据和防治靶点具有重要的理论意义及应用价值。

中文关键词： 高脂膳食；胰岛素抵抗；游离脂肪酸；血管内皮；机制

英文摘要： The cardiovascular diseases（CVD）incidence in our country is consecutively increasing, which ranks the first place in all the diseases causing human death. Arteriosclerosis (AS) is well-regarded as an essential risk reason for CVD. The pathological mechanisms of AS are complex and still not clear so far. Among its risk factors, diet was considered to be an important factor, which was closely with the development of AS. Published reports have shown that high fat diet-induced insulin resistance was an independent risk factor of AS and CVD. The increase of insulin and free fatty acids (FFA) level is a critical pathological feature of insulin resistance. Most researches on the relationship between insulin resistance and AS focused on the lipotoxicity of FFA. Limited study focused on insulin itself on CVD. Moreover, none published study has been reported about the synergetic effects of insulin and FFA on CVD. FFA-induced injury in vascular endothelium is the critical pathological basis in AS. In our previous study, the data showed that insulin could aggravate FFA-induced cell death and adherence factors expression in vascular endothelium cells. Therefore, this item aimed at discovering the synergetic effect of insulin and FFA on the injury of vascular endothelium and uncovering its potential molecular mechanisms via employing in vivo and in vitro experiments. This project will afford new theory and prevention and cure target for AS

英文关键词： high fat diet;insulin resistance;free fatty acid;vascular endothelium;mechanism